Photo-immunotherapy (PIT) is an emerging low-side-effect cancer therapy based on monoclonal antibody (mAb) conjugated with a near-infrared (NIR) phthalocyanine dye (IR700) that induces rapid cellular necrosis after exposure to near infrared light. Although single administration of the therapy (agent + light) was highly effective, recurrences were observed due to the inhomogeneous mAb-IR700 distribution in the tumor. Repeated therapy has shown highly effective tumor treatments owing to the redistribution of antibody into the remnant tumor over time. However, current approach for monitoring IR700 fluorescence signal (macroscopic fluorescence reflectance imaging) lacks the resolution and depth selectivity to reveal mAb-IR700 distribution heterogeneity in situ. As a result, personalized treatment regimen tailored to individual subject is not possible. Real-time monitoring of theranostic agent distribution and therapeutic effects including cellular necrosis, blood flow alterations and stromal changes within the tumor micro-environment will be critical for optimizing the effectiveness of individual PIT treatment. We hypothesize that multi-modal needle imaging technology can provide the information to predict the efficacy of PIT in situ (inside the tumor) and in real-time. The proposed multi-modal optical imaging technology is based on optical coherence tomography (OCT) and fluorescence molecular imaging (FMI). OCT enables high-resolution imaging of tissue microstructures in vivo and has been demonstrated for tumor imaging including tumor boundary detection, lymphangiography and angiography. FMI provides highly sensitive and specific information of the theranostic agent (mAB-IR700) distribution and has been demonstrated for monitoring PIT effects. Our lab has developed an integrated OCT/FMI imaging platform and miniaturized needle imaging devices for OCT and FMI. In this pilot study responding to NCI Omnibus R03, we will investigate the feasibility of multi-modal imaging needle technology for real-time monitoring intra-tumor response to optimize the efficacy of PIT. The specific aims are: 1) Develop multi-channel OCT/FMI imaging needle for real-time monitoring of tumor necrosis, blood flow alteration and tumor cell vitality during PIT at different intra-tumor locations; and 2) Investigate the feasibility of multi-modal intra-tumor imaging for optimizing the therapeutic effects of PIT. This project is a multi-disciplinary collaboration among investigators with expertise in optical imaging (Dr. Yu Chen, UMD) and photo-immunotherapy (Drs. Hisataka Kobayashi and Peter Choyke, NCI). As PIT has emerged as a promising highly selective and clinically feasible theranostic method for treatment of mAb-binding tumors with minimal off-target effects, the proposed multi-channel needle imaging technology will open a window for microscopically monitoring of tumor micro-environment, and will likely be applicable to a wide range of cancer therapies.